The identification and cloning of the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) was a landmark in cystic fibrosis (CF) research. But as soon as the amino acid sequence was deduced several questions were obvious. What is the function of CFTR and how do its different domains control its function? How do CF- associated mutations cause dysfunction in CFTR? How do mutations in CFTR produce the pathogenesis and pathophysiology of the lung disease? These three questions re the focus of this SCOR. The application contains four projects that use basic and clinical research techniques to address the questions. The collaborations and interactions between the investigators on the four projects and the Cell Culture Core provide the best possible environment to increase our understanding of this disease.